In the current year, we have developed a technique that is applicable to microperfusion studies in the dog and will help to study the distal tubular feedback problem. In single nephrons, a wax blocking system has been used to provide a complete and solid block in a proximal tubule. In a segment distal to this block, microperfusion of the distal nephron is initiated. With this microperfusion system, we can change perfusion rate from 10 to 70 nl/min. In an early segment of the proximal tubule prior to the wax block, we can either make complete proximal tubule fluid collections for the measurement of single nephron glomerular filtration rate or measure the stop-flow pressure as an index of glomerular pressure. With this system, we plan to evaluate the effects of increases in distal nephron perfusion rate and perfusate composition on the changes in filtration rate and stop-flow pressure. The presence of a significant decrease in these parameters in response to increases in perfusion rate will provide support for the distal tubular feedback hypothesis. We plan to evaluate the magnitude of these responses to determine if they are sufficient to account for autoregulatory adjustments in renal vascular resistance that are seen at the whole kidney level. We also plan to evaluate the effects of changes in the perfusate composition on these feedback responses in order to determine the possible nature of the feedback mediator. These studies should provide key information related to the role of the distal tubular feedback mechanism in the control of single nephron blood flow and hemodynamics.